This application represents a biological approach to the development of new forms of treatment of opportunistic infections in the acquired immune deficiency syndrome (AIDS). The approach involves five projects which focus on metabolic and biochemical studies of opportunistic fungi and protozoa which will provide important information about their nutrient requirements and lead to the development of new therapeutic targets. Project 1 deals with the development of an axenic culture system for Pneumocystis carinii. Project 2 focuses on the analysis of the transport and metabolism of the lipids of P. carinii. Project 3 involves studies of purine metabolism of Toxoplasma gondii and P. carinii. Project 4 is concerned with D-mannitol metabolism in Cryptococcus neoformans. Project 5 deals with studies of the cytochrome P450 lanosterol 14-alpha-demethylase and NADPH-cytochrome P450 reductase genes of C. neoformans. The application emphasizes close collaboration and communication among investigators so that knowledge gained about one organism can be applied to other opportunistic pathogens.